Crosslinking of allergen to receptor bound IgE activates a signaling cascade in mast and basophil cells that results in the release of chemical mediators responsible for numerous adverse events. For example, such crosslinking leads to the release of preformed mediators of Type I (immediate) anaphylactic hypersensitivity reactions, such as histamine, from storage sites in granules via degranulation. It also leads to the synthesis and release of other mediators, including leukotrienes, prostaglandins and platelet-activating factors (PAFs), that play important roles in inflammatory reactions. Other mediators that are synthesized and released upon allergen crosslinking include cytokines and nitric oxide.
As these mediators are responsible for, or play important roles in, the manifestation of numerous adverse events, the availability of compounds capable of inhibiting the signaling cascade(s) responsible for their release and/or synthesis would be highly desirable.